Thomas Rando

Administrative Appointments

• Director, Rehabilitation Research & Development Center of Excellence, Palo Alto VA Medical Center (2009 - present)
• Deputy Director, Stanford Center on Longevity, Stanford University (2006 - present)
• Director, Geriatric Research, Education, and Clinical Center (GRECC), Palo Alto VA Medical Center (2000 - 2007)
• Founding Director, Muscular Dystrophy Association Clinic, Stanford Medical Center (1999 - 2003)
• Chief, Neurology Service, Palo Alto VA Medical Center (1996 - present)

Honors and Awards

• NIH Director's Pioneer Award, NIH (2005)
• Ellison Medical Foundation Senior Scholar Award in Aging, The Ellison Medical Foundation (2004)
• Paul Beeson Physician Faculty Scholar in Aging, American Federation for Aging Research (1999)
• Frederick E. Terman Fellowship, Stanford University (1996)

Professional Education

Postdoctoral Advisees

Stefano Biressi , Christopher Bjornson , Hiu Tung Cheung , Suchitra Gopinath , Ling Liu , Katie Maguire , Navaline Quach , Marco Quarta , Ann Tang

Graduate & Fellowship Program Affiliations

• Cancer Biology
• Neurosciences

Web Site Links

• http://www.stanford.edu/~casco/

Current Research Interests

Molecular mechanisms of muscle progenitor cell activation: Notch and Wnt signaling

A major interest of the lab is the mechanism by which muscle stem cells are activated to form new muscle during growth, in response to injury, or in disease states. Our recent studies have focused on the Notch and Wnt signaling pathways in these processes. We have found that activation of the Notch signaling pathway is critical to the transition of muscle stem cells ("satellite cells") from a quiescent state to one of active proliferation. The regulation of Notch signaling by its inhibitor Numb appears to determine lineage progression and cell fate determination. Numb is found to be localized asymmetrically in dividing progenitor cells and may be involved in the process of satellite cell self-renewal. We have recently found that activation of the Wnt signaling pathway occurs during muscle injury when satellite cells are proliferating. There appears to be an antagonistic interaction between Notch and Wnt signaling in activated satellite cells during this process. Furthermore, we have found that the age-related impairment of muscle regeneration is due to a decline in effective Notch signaling, manifested initially as a failure of injured muscle to upregulate the Notch ligand, Delta. We are currently exploring further the regulation of the Notch and Wnt signaling pathways during satellite cell activation, the mechanisms underlying the transcriptional control of Delta expression, and epigenetic processes that may account for age-related changes in these pathways. Our near-term goals are to identify the key signaling processes that control satellite cell activation and lineage progression in order to enhance muscle regeneration.

Gene therapy for muscle diseases

Another major focus in the laboratory is gene therapy approaches to the treatment of Duchenne muscular dystrophy (DMD), a degenerative disease of muscle due to mutations in the dystrophin gene that...

Publications

• BCL9 is an essential component of canonical Wnt signaling that mediates the differentiation of myogenic progenitors during muscle regeneration. Brack AS, Murphy-Seiler F, Hanifi J, Deka J, Eyckerman S, Keller C, Aguet M, Rando TA. Dev Biol. 2009; 335 (1): 93-105
• Preventing oxidative stress: a new role for XBP1. Liu Y, Adachi M, Zhao S, Hareyama M, Koong AC, Luo D, Rando TA, Imai K, Shinomura Y. Cell Death Differ. 2009; 16 (6): 847-57
• Biomarker system for studying muscle, stem cells, and cancer in vivo. Nishijo K, Hosoyama T, Bjornson CR, Schaffer BS, Prajapati SI, Bahadur AN, Hansen MS, Blandford MC, McCleish AT, Rubin BP, Epstein JA, Rando TA, Capecchi MR, Keller C. FASEB J. 2009; 23 (8): 2681-90
• Focal adhesion kinase signaling regulates the expression of caveolin 3 and beta1 integrin, genes essential for normal myoblast fusion. Quach NL, Biressi S, Reichardt LF, Keller C, Rando TA. Mol Biol Cell. 2009; 20 (14): 3422-35
• Get personal with gene therapy for muscular dystrophy. Rando TA, Lancet Neurol. 2008; 7 (3): 196-8